Adiponectin: mechanistic insights and clinical implications.

Adiponectin is an adipocyte-derived secretory protein that has been very widely studied over the past 15 years. A multitude of different functions have been attributed to this adipokine. It has been characterised in vitro at the level of tissue culture systems and in vivo through genetic manipulation of rodent models. It is also widely accepted as a biomarker in clinical studies. Originating in adipose tissue, generally positive metabolic effects have been attributed to adiponectin. In this review, we briefly discuss the key characteristics of this interesting but very complex molecule, highlight recent results in the context of its mechanism of action and summarise some of the key epidemiological data that helped establish adiponectin as a robust biomarker for insulin sensitivity, cardiovascular disease and many additional disease phenomena.

Adipose tissue mass and location affect circulating adiponectin levels.

AIMS/HYPOTHESIS: Plasma levels of adiponectin are inversely associated with body mass. We hypothesised that adipose tissue distribution and body composition influences adiponectin levels. METHODS: We assessed plasma adiponectin concentrations and dual-energy X-ray absorptiometry (DEXA) measurements of body composition among 2,820 participants from the Dallas Heart Study. RESULTS: Among both women and men, adiponectin levels were higher in whites than in either Hispanics or African-Americans (for women: median 9.99 µg/ml [25th,75th percentile 7.11, 13.77] vs 7.56 µg/ml [5.05, 9.98] vs 6.39 µg/ml [4.37, 9.41], respectively, p < 0.0001; for men: 6.43 µg/ml [4.66, 9.19] vs 5.55 µg/ml [3.64, 7.50] vs 5.03 µg/ml [3.39, 7.28], p < 0.0001). In univariate analysis, each individual component of body mass was inversely associated with adiponectin. After multivariate analysis, adiponectin levels were found to be positively associated with lower extremity fat, whether expressed in absolute mass (for women: ß = 0.055, p < 0.0001; for men: ß = 0.061, p < 0.0001), or as a relative proportion (for women: ß = 0.035, p < 0.0001; for men: ß = 0.034, p < 0.0001). This association was consistent across ethnicities. Conversely, adiponectin was negatively correlated with truncal fat, both in absolute (for women: ß = -0.039, p < 0.0001; for men: ß = -0.044, p < 0.0001) and relative terms (for women: ß = -0.027, p < 0.0001; for men ß = -0.033, p < 0.0001). At the extreme of body mass, higher degrees of lower extremity and truncal adiposity were associated with higher levels of adiponectin. CONCLUSIONS/INTERPRETATION: These data suggest that the location of adipose depots differentially influences circulating adiponectin concentrations-a finding observed across ethnicity and sex. Gross measures of body mass alone do not adequately account for adiponectin levels. This supports a role of adiponectin as a mediator of the positive effects of lower extremity adiposity on improvements in insulin sensitivity.